Altered hippocampal network excitability in the hypernoradrenergic mutant mouse tottering.
A latent, gene-linked alteration of hippocampal network excitability in tg/tg mutant mice was unmasked in vitro by convulsant-activated synchronous neuronal discharges. Exposure to elevated extracellular potassium ions or 4-aminopyridine, but not picrotoxin, revealed an abnormally prolonged network discharge duration in the mutant CA3 pyramidal cell region. In both phenotypes, noradrenaline, and a selective beta-noradrenergic receptor agonist, isoproterenol, reversibly accelerated the frequency of the discharges. These findings identify an intrinsic alteration in the excitability of an isolated neuronal network in a model of inherited generalized spike-wave epilepsy, and further implicate noradrenergic mechanisms in the temporal modulation of hippocampal synchronization and epileptogenesis.
Noebels
J L
JL
Department of Neurology, Baylor College of Medicine, Houston, TX 77030.
Rutecki
P A
PA
D000818:Animals; D003292:Convulsants / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D008818:Mice, Neurologic Mutants / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011712:Pyramidal Tracts / Q000187:drug effects / Q000502:physiology; D012016:Reference Values
D003292:Convulsants; D007545:Isoproterenol; D009638:Norepinephrine; D010852:Picrotoxin; D011188:Potassium; D011433:Propranolol